CEDAR 150998-005 and SEQUOIA 150998-006
Protocol Amendment Summary
•Protocol Amendment 2
•April 2016
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Protocol Amendment Summary Amendment 2
Title: Safety and Efficacy of Abicipar Pegol (AGN150998) in Patients With Neovascular Age-related
Macular Degeneration
Protocol 150998-005 and 150998-006 Amendment 2
Date of Amendment: April 2016
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Amendment Summary
This summary includes changes made to Protocol 150998005/150998-006 Amendment 1 (approved March 2015).
Following is a summary of content-oriented changes that
were made to each section of the protocol, and a brief
rationale for these changes.
Minor editorial and document formatting revisions have not
been summarized.
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Summary of Changes
Section
Revision
Rationale
Title Page (page 2)
Updated title of Allergan Signatory
Administrative change
Protocol Summary,
Duration, Visit Schedule,
General Statistical
Methods and Types of
Analyses;
Figure 1;
Sections 3, 5.6.2, 6.4.3.1,
7, 8.3.20, 8.7
Updated study duration from 100 to
104 weeks throughout protocol to
reflect change in study duration
Based on the MHRA’s comment to
have last follow up visit occur at least
5 human vitreous half-lifes of the
study drug, either abicipar or
ranibizumab, whichever is longer.
Abicipar’s vitreous half-life is longer
than ranibizumab, it is estimated to
be 12 days.
Protocol Summary,
Endnote;
Table 1, footnote “l”;
Sections 5.6, 5.9
Clarified that preparation for all
treatment administration procedures,
including sham injections, will follow
a standard protocol defined in
procedure manual
Clarification that details of the pretreatment patient preparation
procedure are provided in the
procedure manual
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Summary of Changes
Section
Revision
Rationale
Protocol Summary, Key
Ocular Inclusion Criteria
(study eye);
Section 4.3, Criterion 4
Revised inclusion criterion as follows: Presence of
active subfoveal and/or juxtafoveal CNV (1 to 200
micron from the center) secondary to AMD
assessed by fluorescein angiogram. In addition,
presence of retinal fluid on optical coherence
tomography (OCT) and/or fluorescein leakage
under the fovea as assessed by the investigator at
screening and confirmed by the central reading
center prior to baseline (day 1).
Revised language for
purposes of clarification
only
Protocol Summary, Key
Ocular Exclusion
Criteria (either eye);
Section 4.4, criterion 8
Revised exclusion criterion as follows: Active
periocular, ocular, or /intraocular infection at
baseline (day 1)
Revised language for
purposes of clarification
only
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Summary of Changes
Section
Revision
Rationale
Protocol Summary,
Key Ocular
Exclusion Criteria
(study eye);
Section 4.4,
criterion 18
Revised exclusion criterion as follows: Previous or
concurrent macular laser treatment for macular drusen
Revised language for
purposes of clarification
only
Protocol Summary,
Key Ocular
Exclusion Criteria
(study eye);
Section 4.4,
criterion 21
Revised exclusion criterion as follows: Structural
Revised language for
damage to the center of the macula that is likely to
purposes of clarification
preclude improvement in BCVA following the resolution
only
of macular edema, including atrophy of the RPE, or
retinal fibrosis/scarring as assessed by the investigator
at screening and confirmed by the central reading center
prior to baseline (day 1) including any of the following:
 Macular hole stage 3 or 4
 Atrophy of the RPE
 Retinal fibrosis or scarring
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Summary of Changes
Section
Revision
Rationale
Table 1
Added week 104 as study exit or
early termination visit, week 100 will
be a study assessment visit without
study treatment for all treatment
groups
Based on the MHRA’s comment to have last follow
up visit occur after at least 5 human vitreous halflifes of the study drug, either abicipar or
ranibizumab, whichever is longer. Abicipar’s
vitreous half-life is longer than ranibizumab, it is
estimated to be 12 days.
Table 1
Visit windows for weeks 4 through
24, weeks 28 through 48, weeks 52
through 96, and weeks 100 through
104/early exit has been changed
from ±5 days to ±7 days;
accompanying footnote “p” was
updated to include that the minimum
interval between 2 study visits ≥ 20
days.
The visit windows have been updated to
accommodate site operations; while all indicated
study procedures (including study treatment
administration) are intended to be completed in the
same visit, this footnote clarifies post-baseline visit
dates and visit windows, in particular if the study
treatment is administered on a different day as the
other baseline (day 1) procedures and further
clarifies that the minimum interval between 2 study
visits should be at least 20 days.
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Summary of Changes
Section
Revision
Rationale
Table 1
The timing for specular microscopy (at selected sites) The timing for specular
was set to a fixed visit at week 32. The accompanying microscopy has been set to a
footnote “i” was updated to reflect this change
fixed visit for consistency across
sites
Section 1
Updated to include additional support for dosing
regimens used in the study
Revised language for purposes of
clarification only
Section 3
Updated the minimum and maximum number of visits
scheduled
Revised based on adding visit at
week 104
Section 3.1
Updated to include purpose of monitoring.
Revised language for purposes of
clarification only
Section 4.4,
criterion 3
Updated exclusion criterion to refer to povidone iodine
solution
Revised language for purposes of
clarification only
Section
4.5.1.1
Updated to include use of condoms as preferred
method of contraception for male patients participating
in the study
To specify male contraceptive
measures
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Summary of Changes
Section
Revision
Rationale
Section 4.5.2 Removed topical ocular corticosteroids from prohibited
medication list
Use of topical ocular
corticosteroids is not
likely to impact study
outcome
Section 5.6.2 Added clarification to criteria for escape to standard of care
as follows: Persistent fluid (subretinal and intraretinal) by
OCT, judged to be the cause of the BCVA loss (not explained
by reasons other than the progression of neovascular AMD)
Revised language for
purposes of clarification
only
Section 5.6.2 Updated as follows: Patients who escape to standard of care
will be required to complete the study exit procedures
indicated at the week 100 104/early exit visit and will be
reevaluated at the subsequent follow-up visits: 1) 4 or 8
weeks after receiving first standard-of-care treatment for
BCVA, CRT, and adverse event assessments, 2)
approximately 16 weeks after the last study medication
injection for immunogenicity, BCVA, CRT, and adverse events
assessments, and 3) approximately 52 and 100 weeks after
baseline for BCVA, CRT, and adverse event assessment.
Revised to include
evaluation at
approximately 52 and 100
weeks after baseline
based on DSMC
recommendations.
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Summary of Changes
Section
Revision
Rationale
Section
6.4.3.4
Added: In addition, a post-injection safety follow-up phone
call (up to 3 days following the office visit) should be
performed for all enrolled patients after the administration
of each study treatment. The post-injection safety followup may be completed in-office for patients who participate
in blood sample collection for PK analysis.
Added for consistency with
other sections of protocol
Section 7.3.1
Added that if non-inferiority for both abicipar arms is
established, that superiority testing of abicipar over
ranibizumab will be performed
Updated to reflect changes
to the statistical analysis
plan
Section 7.3.2
Analysis updated to be based on ANCOVA with baseline
BCVA as a covariate
Updated to reflect changes
to the statistical analysis
plan
Section 7.3.3
Updated to describe additional analyses if non-inferiority
for both abicipar arms is established
Updated to align with FDA’s
comments at the end-ofPhase 2 meeting
Section 7.3.4
Removed reference to SAS®
This detail is covered in
statistical appendix
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Summary of Changes
Section
Revision
Rationale
Sections 8.3.1,
8.3.7, 8.3.13,
and 10.4.1
Revise 3-field color imaging to Field 2 for each
mention of dilated color fundus photography
(screening and week 24, 52, and source
documents)
For consistency with the
requirement stated in central
reading center charter
Sections 8.3.9,
8.3.11, and
8.3.13
Removed specular microscopy at weeks 28, 36, 40, For consistency with change to
44, 48, 52.
Table 1
Section 8.3.10
Revised specular microscopy to be prior to study
medication administration at week 32
For consistency with change to
Table 1
Section 8.3.19
Updated week 100 visit procedures to reflect
changes to Table 1 based on addition of week
104/exit visit
For consistency with changes to
Table 1 and addition of week
104/early exit
Section 8.3.20
New section to list visit procedures at week
104/early exit
For consistency with changes to
Table 1 and addition of week
104/early exit
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Summary of Changes
Section
Revision
Rationale
Section 8.7
Updated as follows: Patients who discontinue early due to
other reasons will be required to complete the study exit
procedures indicated at the week 104/early exit visit and will
be reevaluated at the subsequent follow-up visits: 1)
approximately 16 weeks after the last study medication
injection or 100 weeks from baseline whichever occurs
earlier for immunogenicity, BCVA, CRT, and adverse events
assessments, and 2) approximately 52 and 100 weeks after
baseline for BCVA, CRT, and adverse event assessments.
Revised to include
evaluation at approximately
52 and 100 weeks after
baseline based on DSMC
recommendations
Section
10.5.3
Added the following: If local policy does not allow storage of
used study medication vials, the site may destroy the used
vials per their local policy, but must keep the kit box for the
detailed inventory of the study medication.
Revised language for
accommodating the local
policy of handling the used
study medication
Section
12.1
Added abbreviations for the following: ANCOVA, PDT, and
PEG
Included abbreviations that
were either added or not
previously defined.
Note: Stricken text was removed and underlined text was added
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Thank you
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